Tight junctions create the major barrier to paracellular transport across epithelia (Anderson & Van Itallie, 2008) and their permselective properties are quite variable among epithelia. Variations are observed in electrical resistance, ionic charge selectivity and the size-dependence of solute permeability. These properties are the passive complement to active transcellular transport in determining overall transepithelial movement of ions and solutes. There are over 40 different tight junction proteins and consensus is emerging about the contribution of some of these to defining barrier properties (Van Itallie & Anderson, 2006). The continuous cell-cell adhesive seal is formed by members of the large family of claudin transmembrane proteins. Claudins also determine ionic charge selectivity through electrostatic effects of their extracellular protein sequences. Permeability depends strongly on solute size and can be modeled as having two components. Solutes which are smaller than ~4Å in radius pass through a higher capacity system of charge-selective pores which are presumably formed by claudins. Permeability for larger solutes is independent of ionic charge and size and speculated to follow breaks in the cell-cell contacts (Van Itallie et al., 2008). The magnitude of the second pathway is controlled by cytoplasmic coupling to the scaffolding proteins like ZO-1 and the perijunctional actin-myosin cytoskeleton. This presentation will review current ideas about how selectivity of paracellular transport is defined and regulated by specific tight junction proteins and signaling pathways.
Newcastle University (2009) Proc Physiol Soc 16, SA14
Research Symposium: Creating selectivity in paracellular transport
J. M. Anderson1
1. Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
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